The dissertation is devoted to the substantiation of complex treatment of endo-thelial dysfunction of patients with non-alcoholic fatty liver disease with overweight and obesity on the basis of establishing regularities of metabolic disorders of the liv-er. New effective methods of pharmacological correction, timely diagnosis and prog-nosis of the disease have been developed.
The hepatoprotective and endothelioprotective effects of angioline were first discovered. The cell cycle of hepatocytes was analyzed in NAFLD modeling. The normalization of the structural com-ponents of the organ particles occurs under the influence of the active substance. The use of angioline prevents and reduces damage to membrane structures: the nuclear and plasma membranes of endothelial cells and hepatocytes.
The cell cycle of hepatocytes was analyzed in NAFLD modeling. The organo-protective efficiency of angioline in the correction of liver steatosis has been proved. The normalization of the structural components of the organ particles occurs under the influence of the active substance. The use of angioline prevents and reduces dam-age to membrane structures: the nuclear and plasma membranes of endothelial cells and hepatocytes. The ultrastructure of sinusoidal hemocapillaries is enhanced, which stimulates hemodynamics and transcapillary metabolism in the liver, which prevents damage to hepatocyte nuclei and organs, and promotes intracellular regeneration.
Using the biologically active compound angiolin for the correction of experi-mental steatohepatitis leads to a decrease in cytolysis syndrome, leads to normalization of liver function, improves intracellular regeneration of hepatocytes, liver endothelial cells. The combined correction of the steatohepatitis model has shown the greatest ef-fectiveness in normalizing carbohydrate, lipid metabolism and endothelial function.
Hepatocyte cell cycle was first analyzed in NAFLD modeling. The cell cycle of rat liver cells, which was modeled on non-alcoholic fatty liver disease, has its own peculiarities: the number of cells in the synthetic period of the cell cycle (phase S) is higher than in intact animals. Increased DNA fragmentation and proliferative activity of liver cells were found. (p <0.05). The anti-apoptotic effect of the new active sub-stance angiolin has been proved.
The efficacy of the combination of thiotriazoline and L-lysine of escinate has been proved both for the correction of endothelial dysfunction and for the pathoge-netic influence on the development of NAFLD. It was found that the biologically ac-tive compound (S) -2,6-diaminohexanoic acid 3-methyl-1,2,4-triazolyl-5-thioacetate at a dose of 50 mg / kg has a high hepatoprotective activity, reduces cytolysis syn-drome, cholestasis syndrome, increases adiponectin levels and lowers ET-1, which provides useful properties in the treatment of NASH. The revealed properties of An-giolin allow to carry out effective therapy of experimental liver damage - NAFLD.
The appointment of thiotriazoline in the scheme of treatment of patients with non-alcoholic fatty liver disease in statistically significant contributes to the reduction of elevated levels of endothelin-1, indicators of lipid peroxidation, which indicates the need for the use of thiotriazoline as a component of NAFLD treatment. Complex therapy with thiotriazoline and L-lysine escinate is an effective way of eliminating endothelial dysfunction, as evidenced by the reduction of markers of endothelial dys-function: endothelin-1 and Willebrand factor and marker of the inflammatory re-sponse of hs C-reactive protein.
A new non-drug method for the correction of pathological conditions with NAFLD is proposed, which leads to a decrease in the fat component and inflamma-tion, respectively. Non-drug treatment, in addition to basic NAFLD therapy in indi-viduals with overweight and obesity, has a complex, multicomponent, including li-pid-correcting effect. The inclusion of a specially selected set of physical exercises, strictly specific to a particular patient, allows to increase the functional capacity of the patient, to reduce the clinical manifestations of the disease, to prevent complica-tions.
Formation of non-alcoholic fatty liver disease is predicted by determining the sex-specific classification index (Df1 and Df2) by the models obtained on the basis of discriminant analysis.
The proposed method for the diagnosis of non-alcoholic fatty liver disease during prophylactic examination improves the prognosis with high probability of having NAFLD on the first visit of the patient after measuring certain anthropometric parameters of patients, substantiates the need and the amount of additional examina-tion to identify details of the disease.
